Metastatic Lung Adenocarcinoma, Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Adenocarcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8
Conditions
Brief summary
This trial studies the side effects of pembrolizumab with or without chemotherapy in treating patients with stage IV non-small cell lung cancer that has come back (recurrent) and has spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with or without chemotherapy may shrink the tumor in older patients with non-small cell lung cancer.
Detailed description
The primary and secondary objectives of the study: PRIMARY OBJECTIVE: I. To estimate the adverse event profile of MK-3475 (pembrolizumab) in non-small cell lung cancer patients who are age 70 years of age or older and who are treated with MK-3475 (pembrolizumab) +/- chemotherapy in a first-line setting. SECONDARY OBJECTIVES: I. To estimate overall survival. II. To describe patient quality of life during the treatment using the Linear Analogue Self-Assessment (LASA) questionnaire. III. To explore whether Comprehensive Geriatric Assessment (CGA) -derived risk score is able to predict rates of severe adverse events in older cancer patients who receive MK-3475 (pembrolizumab) or MK-3475 (pembrolizumab) + chemotherapy. OUTLINE: Patients are assigned to 1 of 2 groups. GROUP A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. GROUP B: Patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV per institutional guidelines on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up annually for up to 5 years after registration.
Interventions
DRUGPembrolizumab
Given IV
DRUGPemetrexed
Given IV
DRUGCarboplatin
Given IV
OTHERComprehensive Geriatric Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
OTHERQuality-of-Life Assessment
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documentation of Disease: Histologic or cytologic diagnosis of non-small cell lung cancer (adenocarcinoma). Stage IV or recurrent metastatic non-small cell lung cancer. No planned initiation of definitive (potentially curative) concurrent chemo-radiation * Planning to begin MK-3475 (pembrolizumab) treatment within 14 days of registration, with or without combination chemotherapy. Treating physician considers pembrolizumab as appropriate and plans to proceed with one of the following treatment schedules: * MK-3475 (pembrolizumab) 200 mg IV flat dose every 21 days or 400 mg IV every 42 days. * MK-3475 (pembrolizumab) 200 mg IV or 400 mg IV + carboplatin area under the curve (AUC) = 5 + pemetrexed 500 mg/m\^2 (20% chemotherapy dose reduction is permitted per the discretion of the treating physician) * Patients will be ineligible if they have an autoimmune disorder, are post-organ transplantation, or are receiving ongoing immunosuppression treatment * Prior adjuvant therapy is allowed and must have been completed at least 6 months prior to registration * No planned radiation or other cancer treatment in the 3 months following registration * No untreated brain metastases. Patients must be off corticosteroids and asymptomatic at registration * Absolute neutrophil count (ANC) \>= 1500/mm\^3 (1.5 x 10\^9/L) * Platelet count: \>= 100,000/mm\^3 (100 x 10\^9/L) * Creatinine \>= 30 mL/min\* for patients enrolled to pembrolizumab alone and \> 45 mL/min for patients enrolled to chemotherapy + pembrolizumab \* Calculated using the Cockcroft-Gault formula * Total serum bilirubin =\< 1.5 upper limit of normal (ULN) (\< 3 ULN if Gilbert's disease) * Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 3 x ULN (=\< 5.0 x ULN if liver metastases present) * Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN if bone or liver metastases present) Language: Patients must be able to speak and comprehend English in order to complete the mandatory patient-completed measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Grade 3 or Worse Adverse Events Post Registration | Up to 7 days of last day of treatment, up to 6 months | Assessed by National Cancer Institute Common Terminology Criteria in Adverse Events version 5.0. The proportion of patients experience grade 3 or worse adverse events (AEs) will be summarized by frequency and percentage along with a 95% confidence interval (CI) separately by type of therapy (monotherapy or combination therapy) as well as combining the two cohorts. All other individual AEs will be analyzed in an exploratory and hypothesis generating manner; including and not limited to multi-variate logistic regression models considering the baseline demographics and the presence/absence of the AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From study registration to death or the last follow-up whichever occurs first, assessed up to 3 years | Will be summarized using the Kaplan-Meier estimator, separately by monotherapy or combination therapy as well as by the combined cohort. |
| Quality of Life (QOL): Linear Analogue Self-Assessment [LASA] Questionnaire | Up to 9 weeks | The overall quality of life score (the first question of the Linear Analogue Self-Assessment \[LASA\] questionnaire) at each time point as well as change from baseline will be summarized by mean (standard deviation), median (range) along with a longitudinal plot. The median quality of life (QOL) change from baseline along with a 95% confidence interval (CI) will be estimated using the Hodges-Lehmann method. The overall quality of life score will be measured on a scale from 0-10, with higher being better. |
| Comprehensive Geriatric Assessment Risk Score | At baseline. Per the protocol section 13.5,Comprehensive geriatric assessment would be examined combined by arm. | The geriatric risk score, measured as low, medium, or high, will be summarized in a 3X2 frequency table with adverse events. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A (Pembrolizumab) Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.\>\> \>\> Pembrolizumab: Given IV\>\>
\>\> Comprehensive Geriatric Assessment: Ancillary studies\>\>
\>\> Questionnaire Administration: Ancillary studies\>\>
\>\> Quality-of-Life Assessment: Ancillary studies | 45 |
| Group B (Pembrolizumab, Pemetrexed, Carboplatin) Patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV per institutional guidelines on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.\>\> \>\> Pembrolizumab: Given IV\>\>
\>\> Pemetrexed: Given IV\>\>
\>\> Carboplatin: Given IV\>\>
\>\> Comprehensive Geriatric Assessment: Ancillary studies\>\>
\>\> Questionnaire Administration: Ancillary studies\>\>
\>\> Quality-of-Life Assessment: Ancillary studies | 56 |
| Total | 101 |
Baseline characteristics
| Characteristic | Group A (Pembrolizumab) | Total | Group B (Pembrolizumab, Pemetrexed, Carboplatin) |
|---|---|---|---|
| Age, Continuous | 80.0 years STANDARD_DEVIATION 5.85 | 77.8 years STANDARD_DEVIATION 5.35 | 76.1 years STANDARD_DEVIATION 4.21 |
| Any Prior Cancer Diagnosed No | 34 Participants | 73 Participants | 39 Participants |
| Any Prior Cancer Diagnosed Yes | 11 Participants | 28 Participants | 17 Participants |
| Cancer Treatment started prior to enrollment No | 39 Participants | 89 Participants | 50 Participants |
| Cancer Treatment started prior to enrollment Yes | 6 Participants | 12 Participants | 6 Participants |
| Concomitant Chemo No | 45 Participants | 60 Participants | 15 Participants |
| Concomitant Chemo Yes | 0 Participants | 41 Participants | 41 Participants |
| Diagnosis of Non-Small Cell Lung Cancer Recurrent Metastatic | 6 Participants | 15 Participants | 9 Participants |
| Diagnosis of Non-Small Cell Lung Cancer Stage IV | 39 Participants | 86 Participants | 47 Participants |
| ECOG Performance Status 0 | 11 Participants | 32 Participants | 21 Participants |
| ECOG Performance Status 1 | 25 Participants | 57 Participants | 32 Participants |
| ECOG Performance Status 2 | 9 Participants | 11 Participants | 2 Participants |
| ECOG Performance Status 3 | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 96 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| PD-L1 Expression | 54.1 Tumor Proportion Score (%) STANDARD_DEVIATION 37.35 | 32.1 Tumor Proportion Score (%) STANDARD_DEVIATION 37.43 | 13.6 Tumor Proportion Score (%) STANDARD_DEVIATION 25.84 |
| Prior Adjuvant Chemo No | 40 Participants | 92 Participants | 52 Participants |
| Prior Adjuvant Chemo Yes | 5 Participants | 9 Participants | 4 Participants |
| Prior Radiotherapy No | 34 Participants | 76 Participants | 42 Participants |
| Prior Radiotherapy Yes | 11 Participants | 25 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 14 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) White | 37 Participants | 82 Participants | 45 Participants |
| Sex: Female, Male Female | 25 Participants | 48 Participants | 23 Participants |
| Sex: Female, Male Male | 20 Participants | 53 Participants | 33 Participants |
| Smoking History No | 3 Participants | 6 Participants | 3 Participants |
| Smoking History Yes | 42 Participants | 95 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 43 | 6 / 54 |
| other Total, other adverse events | 43 / 43 | 53 / 54 |
| serious Total, serious adverse events | 8 / 43 | 6 / 54 |
Outcome results
Primary
Incidence of Grade 3 or Worse Adverse Events Post Registration
Assessed by National Cancer Institute Common Terminology Criteria in Adverse Events version 5.0. The proportion of patients experience grade 3 or worse adverse events (AEs) will be summarized by frequency and percentage along with a 95% confidence interval (CI) separately by type of therapy (monotherapy or combination therapy) as well as combining the two cohorts. All other individual AEs will be analyzed in an exploratory and hypothesis generating manner; including and not limited to multi-variate logistic regression models considering the baseline demographics and the presence/absence of the AE.
Time frame: Up to 7 days of last day of treatment, up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A (Pembrolizumab) | Incidence of Grade 3 or Worse Adverse Events Post Registration | 11 Participants |
| Group B (Pembrolizumab, Pemetrexed, Carboplatin) | Incidence of Grade 3 or Worse Adverse Events Post Registration | 22 Participants |
Secondary
Comprehensive Geriatric Assessment Risk Score
The geriatric risk score, measured as low, medium, or high, will be summarized in a 3X2 frequency table with adverse events.
Time frame: At baseline. Per the protocol section 13.5,Comprehensive geriatric assessment would be examined combined by arm.
Population: Analyzed with both arms combined
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A (Pembrolizumab) | Comprehensive Geriatric Assessment Risk Score | Low Risk Group | 14 Participants |
| Group A (Pembrolizumab) | Comprehensive Geriatric Assessment Risk Score | Medium Risk Group | 15 Participants |
| Group A (Pembrolizumab) | Comprehensive Geriatric Assessment Risk Score | High Risk Group | 4 Participants |
p-value: 0.9829Chi-squared
Secondary
Overall Survival (OS)
Will be summarized using the Kaplan-Meier estimator, separately by monotherapy or combination therapy as well as by the combined cohort.
Time frame: From study registration to death or the last follow-up whichever occurs first, assessed up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (Pembrolizumab) | Overall Survival (OS) | 16.4 months |
| Group B (Pembrolizumab, Pemetrexed, Carboplatin) | Overall Survival (OS) | 29.9 months |
p-value: 0.0385Log Rank
Secondary
Quality of Life (QOL): Linear Analogue Self-Assessment [LASA] Questionnaire
The overall quality of life score (the first question of the Linear Analogue Self-Assessment \[LASA\] questionnaire) at each time point as well as change from baseline will be summarized by mean (standard deviation), median (range) along with a longitudinal plot. The median quality of life (QOL) change from baseline along with a 95% confidence interval (CI) will be estimated using the Hodges-Lehmann method. The overall quality of life score will be measured on a scale from 0-10, with higher being better.
Time frame: Up to 9 weeks
Population: There were 60 patients who had QOL change from baseline to week 9. Per the protocol section 13.5, quality of life would be examined combined by arm.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group A (Pembrolizumab) | Quality of Life (QOL): Linear Analogue Self-Assessment [LASA] Questionnaire | 0.0 score on a scale |